Central nervous Pathology by dr sadaf hussain

The central nervous system (CNS) comprises the brain and spinal cord and is the most complex organ system in the human body. The CNS differs from other organ systems in the variety of functions that it provides and in the localization of these functions to specialized areas of the CNS. The localization of specialized functions means that a relatively small, focal lesion in the CNS can produce a profound deficit, for example, loss of speech. This localization also results in the various populations of neurons within the CNS having unique capabilities and also unique vulnerabilities to disease. For example, Parkinson disease (PD) preferentially affects the neurons of the substantia nigra in the brain stem, while Alzheimer disease (AD) preferentially affects the neurons of the cerebral cortex.

1. Pathology of CNS DR. AYESHA IQBAL

2. Structure of brain

3. Cerebrum- Center for high complex function- memory, learning, emotion , language. Parts- Frontal, Parietal, Temporal & Occipital lobes. Cerebellum- Movement, balance & posture Medulla oblongata- Controls automatic & homeostatic function such as swallowing, digestion, breathing. GM- neural cell bodies It process & stores information WM - nerve fiber Carry information from 1 tract of brain to another.

4. Cells of CNS Neuron Injury- Apoptotsis (Brain tumor) Necrosis (Red neuron- Hypoxic damage) Neuronal loss( neurodegenerative disease) Axonal degeneration Inclusions ( Alzheimer’s – Neurofibrillary Tangles Parkinson’s - Lewy body) Glial cell- Astrocyte- Star shaped Nuclei- round –oval with peripheral nucleoli, Cytoplasm –highly branched Tissue injury- Hypertrophy & hyperplasia (astrogliosis ) Oligodendrocyte- Relatively large cell lymphocyte-like nuclei with perinuclear halo.

5. Ependyma cell Cuboidal to columnar cells having cilia/microvilli lining the ventricle 3) Microglial cell- Act as a macrophage/ monocyte system in the brain infection/injury- Proliferate

6. Disease of CNS Congenital anomalies Perinatal brain injury Trauma Cerebrovascular disease Infection Demyelinating disease Degenerative disease Tumors

7. Congenital anomalies Neural tube defect Anencephaly- absence of cranial vault. Encephalocele- Herniation of brain tissue through defective cranium.

8. Spina bifida occulta- incomplete closing of the vertebra and membranes around the spinal cord. Meningocele – Meninges protude through small opening. Meningomyeocele- Herniation of spinal cord & meningeal tissue through vertebral defect

9. Forebrain anomalies`- Megalencephaly - Volume of brain is abnormally large. Microcephaly - Volume of brain is small. Cause- Chromosomal abnormalities Fetal alcohol syndrome HIV infection acquired in utero. Lissencephaly (Agyria)- ↓ number of gyri or total absence of gyri

10. Polymicrogyria - ↑ number of small irregular gyri Holoprosencephaly- Incomplete seperation of cerebral hemisphere across midline. (Trisomy 13)

11. Neuronal heterotopias- Collection of neuron in abnormal location. (Periventricular- usually WM) Agenesis of corpus callosum-

12. Posterior fossa anomalies Dandy Walker malformation- Enlarged posterior fossa. Absence of cerebellar vermix or Presence in rudimentary form in anterior portion Replaced by large midline cyst lined by ependyma

13. Arnold Chiari malformation- Small posterior fossa Downward extension of vermis or displacement through foramen magnum

14. Hydromyelia- Multisegmental expansion of central canal of spinal cord . Syringomyelia - Formation of fluid filled cleft like cavity in spinal cord .

15. Perinatal brain injury Important cause of childhood neurological disability. Common cause- Maternal disease Placental abnormalities Most Common underlying pathology- Hemorrhage Infraction

16. T rauma Site & consequence- Frontal lobe- Clinically silent Spinal cord- Severely disable Brain stem- Fatal Types of injury- Skull fracture Parenchymal injury Traumatic vascular injury

17. Skull fracture- Cause- Stepping off a lader Fall due to unconsciousness Parenchymal injury- Concussion- Altered consciousness, secondary to head injury. Contusion (Bruise) Coup & Contre-coup injury- When the head is struck ,the impact causes contusion at the point of the contact (coup injury) & on the opposite side of the brain (Contre-coup injury)

18. Diffuse axonal injury During rapid acceleration of head, some parts of the brain can move separately from other parts  destroy axon necessary for brain functioning

19. Epidural hematoma Site - B/w skull & DM Temporal skull fracture ↓ Injury to middle meningeal artery ↓ Extravasation of blood ↓ Seperation of DM from inner surface of skull ↓ Accumulation of blood (Haematoma)

20. Subdural hematoma Si t e -B / w DM & AM Venous bleeding is self limited Sequence- Lysis of clot-1 wk Growth of fibroblast into hematoma  2wks Development of hyalinized connective tissue  1-3 months.

21. Sequelae of brain trauma Post traumatic hydrocephalus Post traumatic dementia Punch drunk syndrome Hydrocephalus Diffuse axonal injury Post traumatic epilepsy Psychiatric disorder

22. Cerebrovascular Diseaese -carcinoma) 3rd leading cause of death (1 st heart disease, 2 nd Cerebral Infraction- Types- (Red infract)-multiple, sometimes confluent petechial haemorrhage, associated with embolic event Non haemorrhagic (pale infract)- associated with thrombosis . Gross- 1 st 6hrs- minimal change 48 hrs-pale, swollen corticomedullary junction –indistinct 2-10 days- gelatinous, friable, distinct infract border. 10 days-3wks- liquefaction begins.

23. M/ E - 1 st 12 hrs- Red neuron (eosinophilic degeneration of neuron) Swelling of astrocyte 48hrs- Neutrophilic infiltration 2-3wks- Macrophage predominant. Lipid laden macrophage Fluid filled cavity After several months- Dense glial scar.

24. Hypertensive Cerebrovascular disease Most important effect of HTN- lacunar infract Slit haemorrhage Hypertensive encephalopathy Lacunar infract- Gross- Single/ multiple cavitary infract (Infract) M/E- Areas of tissue loss with scattered lipid laden macrophage & surrounding gliosis .

25. Hypertensive encephalopathy- Gross- Edematous brain with or without transtentorial or tonsillar herniation. M/E- Petechiae & fibrinoid necrosis of arteriole in GM & WM.

26. Intracranial haemorrhage- Intracerebral haemorrhage- Acute hemorrhage- Extravasation of blood with compression of adjacent parenchyma. Old hemorrhage- Cavitary destruction of brain with rim of brownish discoloration. M/E- Central core- clotted blood Surrounded brain tissue- odematous, anoxic neuronal & glial change. Eventualy edema resolves, pigment & lipid laden macrophage & reactive astrocyte is seen in the periphery of the lesion.

27. Sub arachnoid haemorrhage- Most common cause- Rupture of saccular aneurysm. Saccular aneurysm- Common sites-

28. Morphology- Unruptured anurysm  thin walled, outpouching along the circles of Wilis 2-3cm in diameter Bright red, shiny surface & thin translucent wall. Wall or lumen of aneurysm- Atheromatous plaque, Calcification or thrombotic occlution. The neck of aneurysm  wide/ narrow. Ruptured usually occurs at the apex of sac. The sac is made up of thickened hyaline intima.

29. Vascular malformation- 1)AV malformation 2)Cavernous malformation 3) Capillary telengiectasia 4)Venous angioma (varices)

30. Infection of CNS Meningitis - Infection of meninges Types- Infectious-Acute pyogenic Chronic Asept ic Chemicals- drugs

31. Acute meningitis Cause- Neonate- E . Coli, G-B strep Adolesence & adult- Neisseria meningitidis Elder- Streptococcus pneumoniae, Liesteria monocytogens. Gross- Exudate- within leptomeniges & over the surface of the brain H. influenzae- basal Pneumococcal- over the cerebral convexities near the sagittal sinus.

32. A th i ck l a y er of suppurat i ve exudate covers the brain stem & cerebellum & thickens the leptomeninges

33. M/E- neutrophilic exudate involving the meninges at the left, with prominent dilated vessels. There is edema and focal inflammation in the cortex to the right.

34. Acute focal suppurative Cerebral abscess- Direct implantation of micro organism Local-mastoiditis,Paranasal sinusitis Haematogenous spread- from heart, lung,distal bone or after tooth extraction Predisposing factor- Acute bacterial endocarditis-multiple abscess Congenital cyanotic Heart disease -Rt to Lt shunt Chronic pulmonary sepsis- bronchiectasis Immunosuppression.

35. Gross- There is a liquefactive center with yellow pus surrounded by a thin wall. M/E- Liquefactive necrosis Around the necrosis, exuberent granulation tissue with neovascularization Fibrous capsule Outside the capsule, zone of reactive gliosis with numerous gemistocytic astrocytes.

36. Chronic meningoencephalitis Cause- M .TB Treponema pallidum Borrelia

37. Chronic bacterial meningoencephalitis Tuberculosis Gross- Sub aracnoid space  fibrinoid exudate . Discrete white granules scattered over leptomeninges. Tuberculoma- well circumscribed intraparenchymal mass. M/E- Central core of casseous necrosis surrounded by tuberculous granulomatous reaction. Long standing case- Fibrous adhesive arachnoiditis . In Mycobacterium avium intracellulare complex- Confluent sheets of macrophage filled with organism with little /no granuloma.

38. Neurosyphilis Tertiary stage of neurosyphilis Occurs in 10% of patient with untreated patient. Pattern- 1) Meningovascular neurosyphilis- Chronic meningitis with numerous plasma cell Associated with oblitereted endarteritis 2) Paretic neurosyphilis- Inflammation Parenchymal damage-- Loss of neuron Proliferation of microglia (rod cell) Gliosis Iron deposition

39. 3) Tabes dorsalis- Loss of both axons & myelin in dorsal root Atrophy of dorsal column of spinal cord .

40. Viral meningoencephalitis M/E- Perivascular lymphocyte cuffing Multiple foci of necrosis in GM & WM Neuronphagia- single cell neuronal necrosis with phagocytosis of debris Microglial nodules Severe cases- necrotizing vasculitis with focal haemorrhage.

41. Herpes infection Gross- Extensive destruction of inferior frontal & anterior temporal lobe. M/E- Necrotizing inflammation Perivascular inflammatory infiltrate Cowdry type-1 intranuclear inclusion viral inclusion in neuron & glial cell.

42. CMV infection Occurs- Fetus Immunosuppressed individual Co mm o n - A I DS pati e nt M/E- Prominent cytomegalic cell with intranuclear & intracytoplasmic inclusion.

43. Rabies infection Gross- Intense edema Vascular congestion M/E- Widespread neuronal degeneration Inflammation Negri body (Pathognomic) most severe in brain stem

44. HIV infection M/E- Microglial nodule- near the small blood vessels Multinucleated giant cell

45. Progressive multifocal encephalopathy Cause- JC polyoma Virus Gross- Irregular poorly defined areas of demyelination M/E- Center- Scattered lipid laden macrophage At the edge of the lesion- enlarge oligodendrocytic nuclei with glassy amorphilic viral inclusion. Within the lesion- bizzare giant astrocyte with irregular hyperchromatic nuclei mixed with reactive astrocyte.

46. Sub acute Sclerosing Panencephalitis Cause- Measles virus M/E- Widespread gliosis & myelin degeneration Viral inclusion within nuclei of oligodendrocyte & neuron Inflammation of WM & GM & neurofibrillary tangles.

47. Fungal Meningoencephalitis f r eq u en c y in A I DS pati e nt) Causative organism- Candida Mucor- most common with Diabetic ketoacidosis. Aspergillus Cryptococcus ( Endemic area- Histoplasma Coccidioides Blastomyces

48. Fungal infection- 3 main pattern- Chronic meningitis Vasculitis- frequently seen in mucormycoses & Aspergillous Parenchymal invasion- commonly seen in Candida Cryptococcus

49. Candida – Multiple microabscess with/ without granuloma formation.

50. Cryptococcus- Gross- Multiple small cyst in basal ganglia M/E- Soap bubbles – Gelatinous material within subarachnoid space & small cyst in parenchyma.

51. Others infection Protozoal infection- Malaria Toxoplasmosis Amoebiasis Trypanosomiasis Rickettsial infection- Typus Rocky mounted spotted fever Metazoal disease- Cysticercosis Echinococcosis

52. Toxoplasmosis Gross- Cerebral abscess M/E- Central necrosis surrounded by acute & chronic inflammatory cell Periphery of necrotic foci- Free tachyzoites & encysted bradyzoite. Organism seen by – H & E or Giemsa stain Immunocytochemical stain